Compounds containing carbon-carbon linker as GPR120 agonists

Abstract

The present invention relates to compound of Formula (I) containing carbon-carbon linker, a stereoisomer, a tautomer, a pharmaceutically acceptable salt, a pharmaceutically acceptable solvate, a prodrug, a polymorph, N-oxide, S-oxide, or a carboxylic acid isostere thereof; processes for their preparation; pharmaceutical compositions comprising said compounds; and their use for the treatment of the diseases or disorders mediated by GPR120 receptor.

We claim: 
     
       1. A compound of formula (I); 
       
         
           
           
               
               
           
         
         wherein,
 Ring A and Ring C are pyridyl; 
 Ring B is a (C 6 -C 10 )aryl; 
 
         X is at least one of 
       
       
         
           
           
               
               
           
         
         wherein   represents a point of attachment;
 R is hydrogen or a (C 1 -C 6 )alkyl; 
 
         R 1 , R 2 , and R 3  at each occurrence are independently selected from the group consisting of hydrogen, a halogen, a (C 1 -C 6 )alkyl, a halo(C 1 -C 6 )alkyl, and a 3- to 10-membered cycloalkyl;
 R 4  and R 7  are independently selected from hydrogen and a (C 1 -C 6 )alkyl; 
 R 5  and R 6  are independently selected from the group consisting of hydrogen, a halogen, and a (C 1 -C 6 )alkyl; and 
 m, n and p are each an integer independently selected from 1, 2 and 3; 
 
         wherein,
 the (C 1 -C 6 )alkyl is unsubstituted or substituted with one or more groups independently selected from the group consisting of a halogen, hydroxy, cyano, nitro, (C 1 -C 6 )alkyl, halo(C 1 -C 6 )alkyl, —O(C 1 -C 6 )alkyl, (C 3 -C 5 )cycloalkyl, and (C 6 -C 10 )aryl; 
 the cycloalkyl is a 3- to 10-membered ring, which is unsubstituted or substituted with one or more groups independently selected from the group consisting of (C 1 -C 6 )alkyl, halogen, hydroxy, —O-(C 1 -C 6 )alkyl, (C 3 -C 10 )cycloalkyl, (C 6 -C 10 )aryl, amino, and cyano; and 
 
         the halogen is selected from chlorine, bromine, iodine, and fluorine. 
       
     
     
       2. The compound of Formula (I) according to  claim 1 , wherein Ring B is an unsubstituted or substituted (C 6 -C 10 )aryl. 
     
     
       3. The compound of Formula (I) according to  claim 2 , wherein Ring B is an unsubstituted or substituted phenyl. 
     
     
       4. The compound of Formula (I) according to  claim 2 , wherein Ring B is an unsubstituted or substituted phenyl and R 2  is located at a para position to Ring A and n is 1. 
     
     
       5. The compound of Formula (I) according to  claim 2 , wherein Ring B is phenyl and R 2  is a halogen located at a para position to Ring A and n is 1. 
     
     
       6. The compound of Formula (I) according to  claim 1 , wherein Ring B is an unsubstituted or substituted phenyl, R 2  is located at a para position to Ring A, R 3  is hydrogen, and m & n are 1. 
     
     
       7. The compound of Formula (I) according to  claim 1 , wherein Ring B is unsubstituted or substituted phenyl; R 2  is halogen located at para position to Ring A; R 3  is hydrogen; and m & n are 1. 
     
     
       8. The compound of Formula (I) according to  claim 1 , wherein Ring B is an unsubstituted or substituted (C 6 -C 10 )aryl, and R 1  is a 3- to 10-membered cycloalkyl. 
     
     
       9. A compound of Formula IA; 
       
         
           
           
               
               
           
         
         wherein,
 Ring A and Ring C are pyridyl; 
 Ring B is a (C 6 -C 10 )aryl; 
 R is hydrogen or a (C 1 -C 6 )alkyl; 
 R 1 , R 2 , and R 3  at each occurrence are independently selected from the group consisting of hydrogen, a halogen, a (C 1 -C 6 )alkyl, a halo(C 1 -C 6 )alkyl, and a 3- to 10-membered cycloalkyl; and 
 m, n and p are each an integer independently selected from 1, 2 and 3; 
 
         wherein,
 the (C 1 -C 6 )alkyl is unsubstituted or substituted with one or more groups independently selected from the group consisting of halogen, hydroxy, cyano, nitro, (C 1 -C 6 )alkyl, halo(C 1 -C 6 )alkyl, —O(C 1 -C 6 )alkyl, (C 3 -C 10 )cycloalkyl, (C 6 -C 10 )aryl; 
 the cycloalkyl is a 3- to 10-membered ring, which is unsubstituted or substituted with one or more groups independently selected from the group consisting of (C 1 -C 6 )alkyl, halogen, hydroxy, —O-(C 1 -C 6 )alkyl, (C 3 -C 10 )cycloalkyl, (C 6 -C 10 )aryl, amino, and cyano; and 
 the halogen is selected from chlorine, bromine, iodine, and fluorine. 
 
       
     
     
       10. A compound of Formula IB; 
       
         
           
           
               
               
           
         
         Ring A and Ring C are pyridyl; 
         Ring B is a (C 6 -C 10 )aryl; 
         R is hydrogen or a (C 1 -C 6 )alkyl; 
         R 1 , R 2 , and R 3  at each occurrence are independently selected from the group consisting of hydrogen, a halogen, a (C 1 -C 6 )alkyl, a halo(C 1 -C 6 )alkyl, and a 3- to 10-membered cycloalkyl; 
         R 4  is independently selected from hydrogen and a (C 1 -C 6 )alkyl; 
         R 5  is independently selected from hydrogen, halogen, and a (C 1 -C 6 )alkyl; and 
         m, n and p are each an integer independently selected from 1, 2 and 3; 
       
       wherein,
 the (C 1 -C 6 )alkyl is unsubstituted or substituted with one or more groups independently selected from the group consisting of halogen, hydroxy, cyano, nitro, (C 1 -C 6 )alkyl, halo(C 1 -C 6 )alkyl, —O(C 1 -C 6 )alkyl, (C 3 -C 10 )cycloalkyl, and (C 6 -C 10 )aryl; 
 the cycloalkyl is a 3- to 10-membered ring, which is unsubstituted or substituted with one or more groups independently selected from the group consisting of (C 1 -C 6 )alkyl, halogen, hydroxy, —O-(C 1 -C 6 )alkyl, (C 3 -C 10 )cycloalkyl, (C 6 -C 10 )aryl, amino, and cyano; and 
 the halogen is selected from chlorine, bromine, iodine, and fluorine. 
 
     
     
       11. A compound of Formula IC; 
       
         
           
           
               
               
           
         
         wherein,
 Ring A and Ring C are pyridyl; 
 Ring B is a (C 6 -C 10 )aryl; 
 R is hydrogen or a (C 1 -C 6 )alkyl; 
 R 1 , R 2 , and R 3  at each occurrence is independently selected from the group consisting of hydrogen, a halogen, a (C 1 -C 6 )alkyl, a halo(C 1 -C 6 )alkyl, and a 3- to 10-membered cycloalkyl; 
 R 4  and R 7  are independently selected from hydrogen and a (C 1 -C 6 )alkyl; 
 R 5  and R 6  are independently selected from the group consisting of hydrogen, a halogen, and a (C 1 -C 6 )alkyl; and 
 m, n and p are each an integer independently selected from 1, 2 or 3; 
 
         wherein,
 the (C 1 -C 6 )alkyl is unsubstituted or substituted with one or more groups independently selected from the group consisting of halogen, hydroxy, cyano, nitro, (C 1 -C 6 )alkyl, halo(C 1 -C 6 )alkyl, —O(C 1 -C 6 )alkyl, (C 3 -C 10 )cycloalkyl, and (C 6 -C 10 )aryl; 
 the cycloalkyl is a 3- to 10-membered ring, which is unsubstituted or substituted with one or more groups independently selected from the group consisting of (C 1 -C 6 )alkyl, halogen, hydroxy, —O-(C 1 -C 6 )alkyl, (C 3 -C 10 )cycloalkyl, (C 6 -C 10 )aryl, amino, and cyano; and 
 the halogen is selected from chlorine, bromine, iodine, and fluorine. 
 
       
     
     
       12. A compound of Formula ID; 
       
         
           
           
               
               
           
         
         wherein,
 Ring A and Ring C are pyridyl; 
 Ring B is a (C 6 -C 10 )aryl; 
 
         X is at least one of 
       
       
         
           
           
               
               
           
         
         wherein   represents a point of attachment;
 R is hydrogen or a (C 1 -C 6 )alkyl; 
 R 1 , R 2 , and R 3  at each occurrence are independently selected from the group consisting of hydrogen, a halogen, a (C 1 -C 6 )alkyl, a halo(C 1 -C 6 )alkyl, and a 3- to 10-membered cycloalkyl; 
 R 4  and R 7  are independently selected from the group consisting of hydrogen and (C 1 -C 6 )alkyl; 
 R 5  and R 6  are independently selected from the group consisting of hydrogen, a halogen, and a (C 1 -C 6 )alkyl; and 
 m, n and p are each an integer independently selected from 1, 2 and 3; 
 
         wherein,
 the (C 1 -C 6 )alkyl is unsubstituted or substituted with one or more groups independently selected from the group consisting of halogen, hydroxy, cyano, nitro, (C 1 -C 6 )alkyl, halo(C 1 -C 6 )alkyl, —O(C 1 -C 6 )alkyl, (C 3 -C 5 )cycloalkyl, and (C 6 -C 10 )aryl; 
 the cycloalkyl is a 3- to 10-membered ring, which is unsubstituted or substituted with one or more groups independently selected from the group consisting of (C 1 -C 6 )alkyl, halogen, hydroxy, —O-(C 1 -C 6 )alkyl, (C 3 -C 10 )cycloalkyl, (C 6 -C 10 )aryl, amino, and cyano; and 
 the halogen is selected from chlorine, bromine, iodine, and fluorine. 
 
       
     
     
       13. A pharmaceutical composition comprising at least one of a therapeutically effective amount of the compound according to  claim 1 , a stereoisomer, a tautomer, and a pharmaceutically acceptable salt thereof; and at least one pharmaceutically acceptable carrier or excipient.